The proposed research has as its long term goal a detailed elucidation of the interaction of amino acids and hormones specifically glucagon and insulin in the regulation of gluconeogenesis in physiologic and pathologic circumstances such as diabetes, obesity, exercise, pregnancy, starvation and trauma. Specifically the role of ketones as a possible protein-sparing substrate will be examined in the post- absorptive and fasted state. The gluconeogenic and protein-catabolic effects of physiologic increments in circulating glucagon will be studied in insulin-dependent diabetics. The role of dietary composition (fat vs. carbonhydrate) in the insulin resistance of obesity will be examined in normal weight patients following a 25% increase in body weight while on a high calorie intake. The relative importance of the liver as a site of insulin action will be determined by studying splanchnic and peripheral glucose balance following ingestion of an oral glucose load. In diabetic patients, peripheral and splanchnic amino acid exchange and circulating glucagon levels will be investigated during exercise.